tbuckley/cabot-search huggingface dataset:
AB1167 THE USE OF ORAL AMINO-BISPHOSPHONATES AND CORONAVIRUS DISEASE 2019 (COVID-19) OUTCOMES
Authors: F. Pistillo, M. Rossini, A. Fassio, C. Benini, D. Gatti, G. Adami
Journal: Annals of the Rheumatic Diseases (2022)

Background The determinants of the susceptibility to SARS-CoV-2 infection and severe Coronavirus Disease 19 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events and cancer. Objectives We conducted a population-based retrospective observational case control study with the primary objective of determining if oral N-BPs treatment can play a role in thesusceptibility to the development of severe COVID-19. Methods Administrative ICD-9-CM and ATC data, representative of Italian population (9% sample of the overallpopulation), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis. Patients treated with bisphosphonates (cases) were randomly matched (1:1 ratio) for age, sex and for other clinically relevant variables (presence of treatments other than bisphosphonates and hospitalizations) with all the health-assisted population without this treatment (controls). Results Incidence of Covid-19 hospitalization was 12.32 [95%CI 9.61-15.04] and 11.55 [95%CI 8.91-14.20], of ICU utilization due to COVID-19 was 1.25 [95%CI 0.38-2.11] and 1.42 [95%CI 0.49-2.36] and of all-cause death was4.06 [95%CI 2.50-5.61] and 3.96 [95%CI 2.41-5.51] for oral N-BPs users and non-users, respectively (Figure 1A). Figure 1B Incidence and 95% CI of COVID-19 related events in N-BPs treated and untreated subjects with anti-osteoporotic drugs and without corticosteroids. C. Incidence and 95% CI of COVID-19 related events in N-BPs treated and untreated without previous vertebral or hip fragility fractures. D. Incidence of COVID-19related events in bisphosphonates treated and untreated patients without previous vertebral or hip fracture without corticosteroid prescriptions. Conclusion In conclusion, we found that the incidence of COVID-19 hospitalization, intensive care unit (ICU) utilization and COVID-19 potentially related mortality were similar in N-BPs treated and non-treated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provided real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results strongly support national and international guidelines that advocate against the discontinuation of oral bisphosphonates only for the fear of COVID-19. Disclosure of Interests None declared
AB0101 INCREASED DNA DAMAGE AND LACK OF DNA REPAIR IN FIBROBLAST-LIKE SYNOVIOCYTES OF INDIVIDUALS AT RISK OF DEVELOPING RHEUMATOID ARTHRITIS
Authors: T. de Jong, J. F. Semmelink, R. A. Hoebe, P. Krawczyk, L. van Baarsen
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is a chronic inflammatory immune-mediated disease leading to synovial tissue inflammation and bone destruction. Inflammation-induced DNA damage in fibroblast-like synoviocytes (FLS) is thought to play an important role in RA pathogenesis. However, since a recent functional genomics study revealed a causal role for FLS in the genetic susceptibility of RA and synovial inflammation is absent in autoantibody positive individuals at risk for RA, we aimed to investigate whether DNA damage in FLS is present before onset of disease. Objectives Determine the extent of DNA damage in FLS and their capacity to repair this damage during the earliest phases of systemic autoimmunity. Methods We included individuals with arthralgia who were IgM rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive but without any evidence of arthritis (RA-risk individuals, n=6), RA patients (n=6), osteoarthritis (OA) patients (n=6) and controls without inflammatory disease (n=6). Synovial tissue biopsies were collected either during joint surgery or individuals underwent a mini-arthroscopy of a knee joint. Subsequently, FLS were in vitro expanded upon enzymatic synovial tissue digestion. DNA damage in FLS (passage 6) was assessed by immunofluorescence staining for yH2AX. DNA damage repair was assessed by first irradiating the cells with 1 gray to induce DNA damage and assess yH2AX staining directly and after 3 and 24 hours of culture to allow for DNA repair. Results Preliminary immunofluorescence staining for yH2AX shows that DNA damage is present in RA-risk and RA FLS to more extent compared with FLS from non-inflammatory controls. OA FLS exhibit even more DNA damage and their nuclei show signs of impaired chromosomal segregation, forming micronuclei with high yH2AX staining intensity. Overall, DNA damage repair is slower in FLS from RA-risk individuals, RA and OA patients compared with controls as shown by persistent yH2AX staining after inducing DNA damage. Conclusion These findings reveal increased DNA damage and concomitant impaired DNA repair in FLS of not only patients with synovial inflammation but also in FLS from RA-risk individuals, suggesting that DNA damage is already present in absence of overt synovial tissue inflammation and before clinical disease onset. More research is needed to investigate DNA damage or lack of DNA repair as potential driver in development of RA. Disclosure of Interests None declared
AB0088 DOUBLE-STRANDED DNA BREAKS ARE A MARKER OF THE INFLAMMATORY ACTIVITY OF RHEUMATOID ARTHRITIS
Authors: A. Avdeeva, Z. Verizhnikova, V. Rybakova, V. Kozlova, T. Popkova, A. Lila, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2022)

Background Double-strand DNA breaks (DNA-DSB) are one of the most biologically significant DNA damage lesions that leads to chromosome breakage and/or rearrangement, mutagenesis and loss or gain of genetic information. The phosphorylation of H2AX histone proteins which are located in the vicinity of the DSBs is known as one of the earliest responses to DNA DSBs in cells. Induction of DNA DSBs in live mammalian cells triggers the phosphorylation near the C-terminal of H2AX protein, which results in the phosphorylated form of H2AX, termed yH2AX. [1,2]. Objectives To examine DNA-DSB among patients with systemic autoimmune rheumatic diseases (SARDs) by evaluating phosphorylation yH2AX and 53BP1 at the site of injury. Methods The analysis included 25 patients with SARDs (19 with RA (16 women, Me;IQR the disease duration 60 (20-103) months, DAS28-ESR 5.05(4.06-5.9)); 4 - with systemic lupus erythematosus (4 women, the disease duration 324 (204-372) months, SLEDAI-2K 9.5 (4.5-16.5) and 2 women with Sjogren’s disease. The control group consisted of 14 healthy donors, comparable in gender and age with the examined patients. DNA-DSB breaks were determined as a discrete focus during immunofluorescence staining with anti-yH2AX and anti-53BP1 antibodies of the lymphocyte culture, followed by analysis on the automated platform AKLIDES (Medipan, Berlin/Dahlewitz, Germany). Results There were no significant differences in the number of DNA breaks among patients with SARDs and healthy donors (p&gt;0.05). There was a positive correlation between % pos. cells by yH2AX and CDAI (r=0.45 p=0.035), Nuclei with foci by 53BP1 and ESR (r=0.53 p=0.02) and IgM RF (r=0.63 p=0.005). Among patients with high CDAI activity (n=10), there was a greater number of Nuclei with foci by yH2AX - (22.5 (6.0-43.0); a higher average number of foci mean (0.39 (0.19-0.62) and a higher % pos. cells (32.6 (18.7-39.1) comparing with patients with low/moderate inflammatory activity (9,0 (2-12); 0,12 (0,02-0,28); 11,5 (1,8-23,5) accordingly, p&lt;0.05, n=9). Conclusion The evaluation of double-stranded DNA breaks can be beneficial as an additional marker for assessing the disease activity among patients with RA. References [1]Reddig A, Voss L, Guttek K, Roggenbuck D et al. Impact of Different JAK Inhibitors and Methotrexate on Lymphocyte Proliferation and DNA Damage. Clinical Medicine. 2021;1;10(7):1431 DOI: 10.3390/jcm10071431 [2]Leifert WR, Siddiqui SM. γH2AX is a biomarker of modulated cytostatic drug resistance. Cytometry A . 2015;87(8):692-5. DOI: 10.1002/cyto.a.22672 Disclosure of Interests None declared
AB0848 ATHEROGENIC INDEX IS THE BEST DETERMINANT OF SUBCLINICAL ATHEROSCLEROSIS IN SPONDYLOARTHRITIS PATIENTS
Authors: A. Ben Tekaya, E. Hannech, A. Fendri, S. Boukriba, O. Saidane, S. Bouden, R. Leila, R. Tekaya, I. Mahmoud, H. Mizouni, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2022)

Background Blood lipid levels particularly total cholesterol (CT), low-density lipoprotein cholesterol (C-LDL), high-density lipoprotein cholesterol (C-HDL), and triglycerides (TG), are commonly used to predict cardiovascular risk. However, it has been demonstrated that atherogenic index (CT/HDL, C-LDL/C-HDL) are prognostic indicators of atherosclerosis [1]. Objectives The purpose of our study was to determine the role of lipid indicators in predicting subclinical atherosclerosis among SpA patients. Methods It was a cross sectional study over a period of 12 months including patients with established SpA (ASAS Criteria). They were cardiovascular disease free. Lipid analyses were performed for all patients including the determination of: C-LDL, C-HDL, CT, and TG. The ratios CT/C-HDL, C-LDL/C-HDL were calculated. Atherosclerosis was assessed by Doppler ultrasound with measurement of the carotid Intima-Media Thickness (cIMT). Results There were 47 SpA patients: 14 female (28.8%) and 33 male (70.2%). The median age was 36 years (18-50). The median disease duration was 11 years (1-32). The median lipid factors levels were respectively 3.66 mmol/l (2.27-6.34) for CT, 0.84 mmol/l (0.43-2.88) for TG, 2.17 mmol/l (0.93-3.9) for C-LDL, and 1.08 mmol/l (0.63-1.49) for C-HDL. The median CT/C-HDL, C-LDL/C-HDL ratios were respectively 3.48 (2.21-6.79) and 1.99 (0.86-3.77). There were 17% of patients with a high ratio CT/C-HDL (&gt;4.5) and 9.3% of patients with high ratio C-LDL/C-HDL (&gt;3.22). The median cIMT was 0.55 millimeters (0.32-0.83). cIMT was positively correlated with low linearity with CT (p=0.007; r=0.404) and with the CT/C-HDL ratio (p=0,028; r=0.34). Conclusion In our study, CT/HDL ratio and CT were the best determinant of subclinical atherosclerosis in SpA patients. References [1]Acevedo M, Krämer V, Tagle R, Corbalán R, Arnaíz P, Berríos X, Navarrete C. Total/HDL cholesterol ratio and non HDL cholesterol as predictors for increased intima media thickness. Rev Med Chil. 2012;140(8):969-76. Disclosure of Interests None declared
AB0737 Capillaroscopic patterns in patients with Systemic Sclerosis- Rheumatoid arthritis (SSc-RA) overlap syndrome.
Authors: O. Desinova, M. Starovoytova, L. P. Ananyeva, O. Koneva, R. Shayakhmetova, L. Garzanova, O. Ovsyannikova
Journal: Annals of the Rheumatic Diseases (2022)

Background Nailfold capillaroscopy is useful for the diagnosis and follow-up of autoimmune rheumatic diseases. Impaired microcirculation is one of the leading factors in local and general pathogenesis of SSc. Nail-fold video-capillaroscopy (NFVC) stands as the most informative and at the same time simple method used for evaluation of capillary circulation. Objectives To identify characteristic and specific for SSc-RA capillaroscopic features. Methods Both hand II – V fingers of 32 pts with SSc-RA were subjected to widefield NFC, evaluated using a binocular 20x magnification Olympus microscope and analyzed in view of specific skin lesions discriminating diffuse and limited SSc forms. Results SSc-specific dilatations of capillary loops were the most common for SSc-RA and were found in all pts SSc-RA. 1/3 pts had signs of active scleroderma pattern, such as capillary loss or “avascular areas” (37,5%) and hemorrhages (28%). The morphological capillary abnormalities such as varying degrees of capillary loops tortuosity/vascular inhomogeneity were present in 69% of examined nailfolds, branching bushy behavior of capillary loops predominated. Architectural disorientation/disarrangement of capillary loops was seen in 37,5% of them. Mega-capillaries and formation of subcutaneous plexus were presented infrequently in 16%. Ramified/bushy capillaries (p&lt;0.04) were significantly more frequent in patients with lab signs of inflammatory (p&lt;0.03). Conclusion Thus, widefield NFVC revealed a “mixed” nature of capillaroscopic changes, combining features specific for SSc (capillary dilation, avascular areas, hemorrhages) and for RA (various changes in capillary loops). Disclosure of Interests None declared
AB0252 INTOLERANCE TO METHOTREXATE IN RHEUMATOID ARTHRITIS: AN ASSESSMENT WITH THE MISS (METHOTREXATE INTOLERANCE SEVERITY SCORE)
Authors: H. Hachfi, S. Abdellatif, M. Brahem, Y. Mohamed
Journal: Annals of the Rheumatic Diseases (2022)

Background Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis (RA), in monotherapy or in combination with biological agents. Its prolonged use requires regular clinical and biological monitoring. The purpose of our study is to assess intolerance to MTX and its consequences. Objectives The purpose of our study is to assess intolerance to MTX and its consequences. Methods This is a cross-sectional study with RA follow-up patients meeting the ACR/EULAR 2010 criteria. An assessment of MTX intolerance was conducted using the Arabic version of the MISS (Methotrexate Intolerance Severity Score). It is a questionnaire containing 12 items covering four areas: abdominal pain, nausea, vomiting and behavioral disorders. A score of six indicates an intolerance. Results Forty patients were included: 35 women (87.5%) and 5 men (12.5%) of average age 51.7 years ±12.7 years. The average duration of disease progression was 12.2 years 9.2 [1-40 years]. All patients were treated with methotrexate and supplemented with folic acid. 50% of patients were under 10mg/week of MTX, 27.5% under 15mg/week and 22.5% under 20 mg/week. Patients had been on this treatment for an average of 8.7 years [1-25 years]. The majority of them (97.5%) received corticosteroids in combination, 12.5% received Salazopyrine and 27.5% received biotherapy. Methotrexate intolerance was observed in 16 patients (42.1%). Nausea was observed in 13 patients (81.2%), vomiting in 5 patients (31.2%), abdominal pain in 11 patients (68.8%) and behavioral disorders in all patients. As a result of this intolerance, 18.8% of patients had to stop their treatment, 12.5% decreased the dose on their own, 6.2% took the MTX irregularly, 12.5% switched from the oral route to the intramuscular route and 50% continued to take their treatment in the usual way. The study of correlations did not reveal statistically significant associations between MTX intolerance and age, sex, dose and duration of MTX, the associated intake of salazopyrin, biotherapy and other symptomatic treatments. Conclusion The occurrence of an intolerance to MTX is common in patients followed for RA, which may lead to poor adherence to therapy or even a discontinuation of treatment thus decreasing the effectiveness of management. Hence the need to systematically detect this intolerance and react in time. Disclosure of Interests None declared
AB0468 COMPARISON OF THE DIAGNOSTIC PERFORMANCE OF SALIVARY GLAND SCINTIGRAPHY AND ULTRASOUND IN SJÖGREN’S SYNDROME
Authors: M. I. González-Nieto, A. Portella Alegre, A. García-Burillo, S. Asadurova, J. Mestre-Torres, X. Serres-Créixams, R. Solans-Laqué
Journal: Annals of the Rheumatic Diseases (2022)

Background The 2002 American-European Consensus Group (AECG) criteria included salivary gland scintigraphy (SGS) as one of the possible objective methods for assessing salivary gland involvement in primary Sjögren’s syndrome (pSS). However, this test as well as the sialography were not included in the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria and considered obsolete. On the other hand, salivary gland ultrasound (SGUS) is a simple and non-invasive procedure that is readily available and provides important information on the major salivary glands. Several recent studies have assessed SGUS as a tool for diagnosing pSS. Objectives To compare the diagnostic performance of SGS and SGUS for pSS patients. Methods We included 63 patients with sicca symptoms and suspected pSS. Diagnosis of pSS was established following the 2002 AECG criteria. The patients’ scintigraphic grade was determined according to Schall classification (I-IV scale) [1], establishing Schall grade ≥III (moderate functional impairment) as the cut-off. We considered SGUS score based on parenchymal homogeneity, presence of hypoechogenic areas, and clearness of posterior glandular border of salivary glands. The score of the highest graded gland was considered, and a score ≥2 was defined as a positive SGUS, according to OMERACT US-SG scoring [2]. The area under the receiver operating characteristic (ROC) curve was employed to evaluate the screening method’s performance. Results pSS was diagnosed in 40 (63%) patients, and the remaining 23 sicca subjects (37%) constituted the control group. Abnormal SGS was established in 26/40 (65%) pSS patients and 10/23 (43%) controls. Positive SGUS was established in 24/40 (60%) pSS patients and 6/23 (26%) controls. Thus, the sensitivity and specificity of SGS were 65% and 57%, respectively, and 60% and 74% for SGUS, respectively. The area under the ROC curve (Figure 1) of scintigraphy was 0.73, while for the SGUS was 0.83. Figure 1. ROC curve comparison of SGS and SGUS for the diagnosis of pSS. Conclusion The diagnostic accuracy of SGUS is not only comparable with scintigraphy in pSS patients but also results in a better performance. This result indicates that SGUS is a useful method for evaluating salivary gland involvement in pSS and could be an alternative tool to other diagnostic techniques, such as SGS. References [1]Schall GL, Anderson LG, Wolf RO, Herdt JR, Tarpley TM Jr, Cummings NA, et al. Xerostomia in Sjögren’s syndrome. Evaluation by sequential salivary scintigraphy. JAMA. 1971 28;216(13):2109-16. [2]Jousse-Joulin S, Coiffier G. Current status of imaging of Sjogren’s syndrome. Best Pract Res Clin Rheumatol. 2020;34(6):101592. Disclosure of Interests None declared
AB0021 FEATURES OF IMMUNOLOGICAL MANIFESTATIONS OF СOMMON VARIABLE IMMUNODEFICIENCY COMBINED WITH RHEUMATOID ARTHRITIS
Authors: S. Kudryashov, L. Karzakova, I. Sidorov, N. Zhuravleva
Journal: Annals of the Rheumatic Diseases (2022)

Background The prevalence rate of сommon variable immunodeficiency (CVID), the most common symptomatic form of primary immunodeficiency disease (PID), is growing every year. In the Republican Register of PID in the Chuvash Republic (Russia) there are 32 patients with CVID, 5 (15.6%) of whom have CVID combined with an autoimmune disease - rheumatoid arthritis (RA). The immunological studies occupy a large place in the diagnosis of PID and autoimmune diseases. Objectives The aim of the study was to search for immunological criteria for the differentiation of RA from CVID combined with RA. Methods The object of the study were 2 groups of patients. Group 1 consisted of 20 RA patients; group 2 consisted of 5 patients with CVID in combination with RA. Patients with CVID, who had the results of an immunological study conducted before the appointment of immunoglobulin replacement therapy, were selected for this study. The control group consisted of 20 practically healthy people. Results The significant changes were revealed in the concentration of serum immunoglobulins in the studied groups of patients, in particular, a sharp decrease in IgG levels in group 2 (1.9±0.3 g/l vs. 15.2±2.3 in group 1, p&lt;0.001), IgA (0.1±0.02 g/l vs. 3.1±0.7 g/l in group 1, p&lt;0.001), IgM (0.2±0.03 g/l vs. 1.7±0.2 g/l in group 1, p&lt;0.001). Immunoglobulin levels in both groups of patients were lower (p&lt;0.001) compared to the control group. In both groups, the number of regulatory cells – Treg (CD4+CD25+FoxP3) was reduced: in group 1 - to 2.5±0.03%; in group 2 - to 2.3± 0.02%, while in the control group it was 4.2± 0.5%, p&lt;0.001. The result of our study confirms that the development of RA and CVID is associated with the decrease in the number of Treg cells responsible for ensuring peripheral tolerance and preventing the development of autoimmune diseases. Conclusion CVID and RA have a common immunopathological sign - a decrease in the content of Treg cells in the blood. In the differential diagnosis between RA and CVID, combined with RA, it is necessary to rely on the results of the determination of immunoglobulins in the blood serum. Disclosure of Interests None declared
AB0396 EFFECT OF A MULTIDISCIPLINARY LIFESTYLE PROGRAM IN PATIENTS WITH RHEUMATOID ARTHRITIS: THE PLANTS FOR JOINTS RANDOMIZED CONTROLLED TRIAL
Authors: W. Walrabenstein, C. Wagenaar, M. van der Leeden, F. Turkstra, J. Twisk, M. Boers, H. van Middendorp, P. Weijs, D. van Schaardenburg
Journal: Annals of the Rheumatic Diseases (2022)

Background Lifestyle factors have been associated with the development and progression of rheumatoid arthritis (RA). Interventions involving whole food plant-based diets (WFPDs), physical activity or stress management have shown promising results for people with RA but were not yet evaluated in an integrated program. Objectives To determine the effect of a 16-week multidisciplinary lifestyle program on disease activity in patients with RA. Methods In the “Plants for Joints” (PFJ) parallel-arm, assessor-blind randomized clinical trial, patients with RA and a 28-joint Disease Activity Score [DAS28] score ≥ 2.6 and ≤ 5.1, were assigned to the PFJ group or the control group. The PFJ group followed a lifestyle program based on a WFPD, physical activity, and stress management in addition to usual care. The control group received usual care. Medication was kept stable three months before and during the trial. Secondary outcomes included anthropometric, and metabolic markers. An intention-to-treat analysis with a linear mixed model, adjusted for baseline values was used to analyze between-group differences of continuous outcomes. Results Of 115 people screened, 85 were randomized and 79 completed the study. Participants were 91% female with a mean (SD) age of 55 (12) and body mass index of 26 (4) kg/m 2 . After 16 weeks the PFJ group had a mean 0.85-point greater improvement of the DAS28 versus the control group (95% CI 0.40 to 1.30; p &lt; 0.001) (Figure 1). Subgroup analyses showed significant improvements in the seropositive as well as the seronegative subgroup, although the effect was more profound in the seronegative group. Weight, fat mass, HbA1c, LDL and triglycerides also showed significant improvements in the PFJ versus control group, while blood glucose and HDL remained unchanged (Table 1). No serious adverse events occurred. Conclusion The 16-week PFJ lifestyle program substantially decreased disease activity in people with RA with low-moderate disease activity. Disclosure of Interests Wendy Walrabenstein: None declared, Carlijn Wagenaar: None declared, Marike van der Leeden: None declared, Franktien Turkstra: None declared, Jos Twisk: None declared, Maarten Boers Consultant of: Consultant for Novartis, Henriët van Middendorp: None declared, Peter Weijs: None declared, Dirkjan van Schaardenburg: None declared